Perception of sound is attributed to the pattern of neural activity within the central auditory system. The auditory system is typically defined as a series of structures that are connected directly or indirectly to the cochlea. The significance of a sound, however, depends not only on spectral and temporal characteristics as mediated through the auditory system, but also on the past history and behavioral state of the animal. In other words, sound processing should also include non-auditory systems that would convey sensorimotor functions, emotion, learning, and memory. In this application, we plan to study the nature of non-auditory projections to the cochlear nucleus in order to gain insight into how different systems influence our perception of sound. We propose that the granule cell domain of the cochlear nucleus represents a key site for the integration of mutimodal influences. Preliminary data reveals that somatosensory, vestibular, pontine, reticular, and descending auditory projections access the granule cell domain. We will use anterograde and retrograde tract tracing methods in conjunction with light and electron microscopy to identify projecting neurons and their circuits, immunocytochemical staining procedures to reveal the chemistry of the different terminals, and electrophysiological recording techniques to characterize the response properties of neurons projecting to this region. We will apply nanoparticle technology to explore the use of biodegradable polymers with the goal of creating a new line of neuronal tracers for this study. The possibility of attaching ligands to the surface of the particles could enhance tracer uptake for the selective targeting of specific families of neurons. The data from this research will provide new knowledge on the synaptic organization of a highly integrative structure in the auditory system, and should yield insights into how diverse neural systems shape the coding process for hearing. As we learn about how the somatosensory system modulates hearing, we will gain insight into somatic tinnitus that could contribute to the design of treatment strategies and a better understanding of tinnitus in general. [unreadable] [unreadable] [unreadable]